Alteration of CXCR7 expression mediated by TLR4 promotes tumor cell proliferation and migration in human colorectal carcinoma.

Alteration of CXCR7 expression mediated by TLR4 promotes tumor cell proliferation and migration in human colorectal carcinoma.
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TLR4 介导的 CXCR7 表达改变可促进人结直肠癌中肿瘤细胞的增殖和迁移。

DOI:
10.1371/journal.pone.0027399
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Zhang Y
Zhang Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xu H;Wu Q;Dang S;Jin M;Xu J;Cheng Y;Pan M;Wu Y;Zhang C;Zhang Y

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炎症与结直肠癌之间的联系已被公认。然而,细菌脂多糖(LPS)与Toll样受体4(TLR4)结合对人结直肠癌细胞趋化因子受体的影响尚不清楚。本研究表明,在表达TLR4/髓系分化蛋白(MD-2)的结直肠癌细胞系SW480和Colo 205中,脂多糖暴露可增加CXC趋化因子受体7(CXCR7)的表达。CXCR7与SW480细胞的增殖和迁移有关。而SW480和Colo 205细胞暴露于脂多糖后,CXCR4的表达无明显变化。为了进一步支持上述结果,我们分析了TLR4、MD-2和CXCR7在人结直肠癌组织中的表达。结直肠癌组织中TLR4(53%)、MD-2(70%)和CXCR7(29%)的表达高于正常组织。我们在结直肠癌组织标本中发现TLR4、MD-2和CXCR7的重组与肿瘤大小、淋巴结转移和远处转移密切相关(p = 0.037,p = 0.002,p = 0.042)。因此,联合检测TLR4、MD-2和CXCR7在结直肠癌组织中的表达可能为判断肿瘤生长和转移提供有价值的预后诊断依据。TLR4、MD-2和CXCR7的相互作用可能对结直肠癌的新免疫调节疗法感兴趣。
The link between inflammation and colorectal carcinoma has been acknowledged. However, the impact of bacterial lipopolysaccharide (LPS) binding to Toll-like receptor 4 (TLR4) on chemokine receptors in human colorectal carcinoma cells still remains to be elucidated. The present study shows that exposure to LPS elevated CXC chemokine receptor 7 (CXCR7) expression in colorectal carcinoma SW480 and Colo 205 cell lines expressing TLR4/myeloid differential protein (MD-2). CXCR7 is associated with SW480 cell proliferation and migration. However, exposure of SW480 and Colo 205 cells to LPS had no effect on CXCR4 expression. To further support the above results, the expression of TLR4, MD-2, and CXCR7 was analyzed in human colorectal carcinoma tissues. Higher rates of TLR4 (53%), MD-2 (70%), and CXCR7 (29%) expression were found in colorectal carcinoma tissues than in normal tissues. We demonstrated that the recombination of TLR4, MD-2 and CXCR7 strongly correlated with tumor size, lymph node metastasis and distant metastasis in colorectal carcinoma tissue samples (p = 0.037, p = 0.002, p = 0.042, resp.). Accordingly, simultaneous examination of the expression of TLR4, MD-2 and CXCR7 in cancer tissues of colorectal carcinoma may provide valuable prognostic diagnosis of carcinoma growth and metastasis. Interplay of TLR4, MD-2 and CXCR7 may be of interest in the context of novel immunomodulatory therapies for colorectal carcinoma.
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